Sphingosine-1-Phosphate and Its Receptors: A Mutual Link between Blood Coagulation and Inflammation

Figure 5

Interactions of S1PRs and PARs in monocyte function. In human monocytes, S1P significantly enhances expression of the thrombin receptors PAR-1 and PAR-4 at the mRNA and protein level. Elevation of PAR-1/PAR-4 abundance appears to be mediated via activation of S1PR3 and results in increased migration of the monocyte toward thrombin. These responses are associated with PI3K/Akt-mediated expression of COX-2. At sites of vascular injury, increased levels of S1P, for example, released from aggregating platelets, may enhance the inflammatory response of local monocytes, thereby modulating tissue-targeted events such as thrombosis and vessel injury.